ARACHIDONIC-ACID AND ITS METABOLITES INCREASE CA-I IN CULTURED RAT OLIGODENDROCYTES

Fluorescence measurements of intracellular calcium (Ca(i)) were made on cultured rat spinal cord oligodendrocytes (OLGs) using the dye fura-2. Exposure of OLGs to arachidonic acid (AA) (5-50 muM) elicited a concentration-dependent increase in Ca(i) that was derived mainly from extracellular Ca2+. AA at 50 muM also released Ca2+ from intracellular stores. The response to AA was not decreased by nifedipine or by inhibition of Na+-Ca2+ exchange. AA-induced Ca2+ influx pathway was permeable to Mn2+ and Co2+ but not to Ba2+ and was not markedly influenced by depolarization, suggesting that AA activates a voltage-independent, not strictly selective, Ca2+ channel. The Ca(i) response to AA was partially attenuated in the presence of indomethacin, indicating that the Ca(i) response was mediated in part by cyclooxygenase products of AA. However, the AA-induced Ca(i) response far exceeded that induced by prostaglandins and was mimicked by linoleic acid. We conclude that AA modulates Ca(i) of OLGs via two mechanisms: 1) indirectly via cyclooxygenase pathway and 2) directly via membrane lipid-protein interaction.